Is PDK3 p.Pro68= (c.204G>A) pathogenic?

PDK3 p.Pro68= (c.204G>A) is classified Benign/Likely benign in PDK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-01). Ultra-rare (popmax 0.0332%, afr); Associated with Charcot-Marie-Tooth disease X-linked dominant 6.

What condition is associated with PDK3 p.Pro68= (c.204G>A)?

PDK3 p.Pro68= (c.204G>A) is associated with Charcot-Marie-Tooth disease X-linked dominant 6 (ClinVar).

How common is PDK3 p.Pro68= (c.204G>A) in the general population?

PDK3 p.Pro68= (c.204G>A) is ultra-rare (popmax 0.0332%, afr) (gnomAD).

How is X-linked Charcot-Marie-Tooth disease type 6 inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PDK3 p.Pro68=

c.204G>A · rs201536570 · VCV1164809

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, afr)

Conditions

Charcot-Marie-Tooth disease X-linked dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -5
Overall
CADD	0.734	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0332% African / African-American · 19/57,160 alleles

Filtering AF 0.0217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0181%

Overall 0.00324% 39/1,204,624 alleles · ultra-rare exomes 33/1,092,414 · genomes 6/112,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0332%	3,008
Middle Eastern	0.023%	4,341
Remaining individualsnot grpmax-eligible	0.0127%	7,903
South Asian	0.00711%	14,056
East Asian	0.00297%	33,702
Admixed American	0.00221%	45,289
European (non-Finnish)	0.000785%	127,318

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PDK3
Protein: p.Pro68=
Coding: c.204G>A
MANE Select: NM_005391
dbSNP: rs201536570
Type: single nucleotide variant
Location: chrX:24494839 (GRCh38)
Structure: AlphaFold pLDDT 91.32 · 5 PDB

Full PDK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease X-linked dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked Charcot-Marie-Tooth disease type 6 (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood

Similar variants

PDK3 p.Pro68Leu Uncertain significance ★ ⚠ same residue
PDK3 c.320+6T>C Uncertain significance ★★ same condition
PDK3 p.Ala360Val Uncertain significance ★★ ⚠ same condition
PDK3 p.Arg378Cys Uncertain significance ★★ same condition
PDK3 p.Asp188Asn Uncertain significance ★★ ⚠ same condition
PDK3 p.Ile113Thr Uncertain significance ★★ ⚠ same condition
PDK3 p.Leu112Pro Uncertain significance ★★ ⚠ same condition
PDK3 p.Pro141Leu Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pdk3-p-pro68 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown